The influence of Epstein-Barr virus and cytomegalovirus on childhood respiratory health: A population-based prospective cohort study

Evelien R. van Meel; Vincent W.V. Jaddoe; Irwin K.M. Reiss; Menno C. van Zelm; Johan C. de Jongste; Henriëtte A. Moll; Liesbeth Duijts

doi:10.1111/cea.13579

The influence of Epstein-Barr virus and cytomegalovirus on childhood respiratory health: A population-based prospective cohort study

Evelien R. van Meel, Vincent W.V. Jaddoe, Irwin K.M. Reiss, Menno C. van Zelm, Johan C. de Jongste, Henriëtte A. Moll, Liesbeth Duijts^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Background: Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection are common in early childhood. CMV infection favours a T-helper-1 and EBV infection a T-helper-2 cell response, possibly leading to disbalanced T-helper cell response, and subsequent risk of asthma or atopy. Objective: To study the associations of EBV and CMV with lung function, asthma and inhalant allergic sensitization at school age. Methods: This study among 3546 children was embedded in a population-based prospective cohort. At age 6 years, serum IgG levels against EBV and CMV were measured by ELISA. At age 10 years, lung function was measured by spirometry, asthma by questionnaire and inhalant allergic sensitization by skin prick test. Results: Unadjusted models showed that seropositivity for EBV was associated with a higher FEV₁ and FEF₇₅ (Z-score difference (95% CI): 0.09 (0.02, 0.16) and 0.09 (0.02, 0.15)), while seropositivity for CMV was not. Specific combinations of viruses showed that seropositivity for EBV was only associated with FEV₁ and FEF₇₅ in the presence of seropositivity for CMV (0.12 (0.04, 0.20)) and 0.08 (0.01, 0.15)). Seropositivity for CMV in the absence of seropositivity for EBV was associated with an increased risk of inhalant allergic sensitization (OR (95% CI): 1.31 (1.02, 1.68)). All effect estimates attenuated into non-significant mainly after adjustment for child's ethnicity. Seropositivity for EBV or CMV was not associated with asthma. Conclusions and Clinical Relevance: Associations of EBV and CMV infections in early childhood with school-age lung function and inhalant allergic sensitization are explained by ethnicity, or sociodemographic and lifestyle-related factors.

Original language	English
Pages (from-to)	499-507
Number of pages	9
Journal	Clinical & Experimental Allergy
Volume	50
Issue number	4
DOIs	https://doi.org/10.1111/cea.13579
Publication status	Published - Apr 2020

Bibliographical note

Funding Information:
The Generation R Study is made possible by financial support from the Erasmus Medical Centre, Rotterdam, the Erasmus University Rotterdam and the Netherlands Organization for Health Research and Development. Dr Vincent Jaddoe received an additional grant from the Netherlands Organization for Health Research and Development (ZonMw-VIDI) and the European Research Council (ERC-2014-CoG-648916). Dr Liesbeth Duijts received funding from the European Union's Horizon 2020 co-funded programme ERA-Net on Biomarkers for Nutrition and Health (ERA HDHL) (ALPHABET project (no 696295; 2017), ZonMW The Netherlands (no 529051014; 2017)). The project received funding from the European Union's Horizon 2020 research and innovation programme (LifeCycle project, grant agreement no 733209; 2016). The researchers are independent from the funders. The study sponsors had no role in the study design, data collection and analysis, interpretation of data, writing of this report or the decision to submit the article for publication. The Generation R Study is conducted by the Erasmus Medical Centre in close collaboration with the School of Law and the Faculty of Social Sciences at the Erasmus University, Rotterdam, the Municipal Health Service, Rotterdam area, and the Stichting Trombosedienst and Artsen laboratorium Rijnmond (Star-MDC), Rotterdam. We gratefully acknowledge the contribution of children and their parents, general practitioners, hospitals, midwives and pharmacies in Rotterdam.

Publisher Copyright:
© 2020 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.

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@article{b88d694906874b29be46b9df2b782e28,

title = "The influence of Epstein-Barr virus and cytomegalovirus on childhood respiratory health: A population-based prospective cohort study",

abstract = "Background: Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection are common in early childhood. CMV infection favours a T-helper-1 and EBV infection a T-helper-2 cell response, possibly leading to disbalanced T-helper cell response, and subsequent risk of asthma or atopy. Objective: To study the associations of EBV and CMV with lung function, asthma and inhalant allergic sensitization at school age. Methods: This study among 3546 children was embedded in a population-based prospective cohort. At age 6 years, serum IgG levels against EBV and CMV were measured by ELISA. At age 10 years, lung function was measured by spirometry, asthma by questionnaire and inhalant allergic sensitization by skin prick test. Results: Unadjusted models showed that seropositivity for EBV was associated with a higher FEV1 and FEF75 (Z-score difference (95% CI): 0.09 (0.02, 0.16) and 0.09 (0.02, 0.15)), while seropositivity for CMV was not. Specific combinations of viruses showed that seropositivity for EBV was only associated with FEV1 and FEF75 in the presence of seropositivity for CMV (0.12 (0.04, 0.20)) and 0.08 (0.01, 0.15)). Seropositivity for CMV in the absence of seropositivity for EBV was associated with an increased risk of inhalant allergic sensitization (OR (95% CI): 1.31 (1.02, 1.68)). All effect estimates attenuated into non-significant mainly after adjustment for child's ethnicity. Seropositivity for EBV or CMV was not associated with asthma. Conclusions and Clinical Relevance: Associations of EBV and CMV infections in early childhood with school-age lung function and inhalant allergic sensitization are explained by ethnicity, or sociodemographic and lifestyle-related factors.",

author = "{van Meel}, {Evelien R.} and Jaddoe, {Vincent W.V.} and Reiss, {Irwin K.M.} and {van Zelm}, {Menno C.} and {de Jongste}, {Johan C.} and Moll, {Henri{\"e}tte A.} and Liesbeth Duijts",

note = "Funding Information: The Generation R Study is made possible by financial support from the Erasmus Medical Centre, Rotterdam, the Erasmus University Rotterdam and the Netherlands Organization for Health Research and Development. Dr Vincent Jaddoe received an additional grant from the Netherlands Organization for Health Research and Development (ZonMw-VIDI) and the European Research Council (ERC-2014-CoG-648916). Dr Liesbeth Duijts received funding from the European Union's Horizon 2020 co-funded programme ERA-Net on Biomarkers for Nutrition and Health (ERA HDHL) (ALPHABET project (no 696295; 2017), ZonMW The Netherlands (no 529051014; 2017)). The project received funding from the European Union's Horizon 2020 research and innovation programme (LifeCycle project, grant agreement no 733209; 2016). The researchers are independent from the funders. The study sponsors had no role in the study design, data collection and analysis, interpretation of data, writing of this report or the decision to submit the article for publication. The Generation R Study is conducted by the Erasmus Medical Centre in close collaboration with the School of Law and the Faculty of Social Sciences at the Erasmus University, Rotterdam, the Municipal Health Service, Rotterdam area, and the Stichting Trombosedienst and Artsen laboratorium Rijnmond (Star-MDC), Rotterdam. We gratefully acknowledge the contribution of children and their parents, general practitioners, hospitals, midwives and pharmacies in Rotterdam. Publisher Copyright: {\textcopyright} 2020 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.",

year = "2020",

month = apr,

doi = "10.1111/cea.13579",

language = "English",

volume = "50",

pages = "499--507",

journal = "Clinical & Experimental Allergy",

issn = "0954-7894",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "4",

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TY - JOUR

T1 - The influence of Epstein-Barr virus and cytomegalovirus on childhood respiratory health

T2 - A population-based prospective cohort study

AU - van Meel, Evelien R.

AU - Jaddoe, Vincent W.V.

AU - Reiss, Irwin K.M.

AU - van Zelm, Menno C.

AU - de Jongste, Johan C.

AU - Moll, Henriëtte A.

AU - Duijts, Liesbeth

N1 - Funding Information: The Generation R Study is made possible by financial support from the Erasmus Medical Centre, Rotterdam, the Erasmus University Rotterdam and the Netherlands Organization for Health Research and Development. Dr Vincent Jaddoe received an additional grant from the Netherlands Organization for Health Research and Development (ZonMw-VIDI) and the European Research Council (ERC-2014-CoG-648916). Dr Liesbeth Duijts received funding from the European Union's Horizon 2020 co-funded programme ERA-Net on Biomarkers for Nutrition and Health (ERA HDHL) (ALPHABET project (no 696295; 2017), ZonMW The Netherlands (no 529051014; 2017)). The project received funding from the European Union's Horizon 2020 research and innovation programme (LifeCycle project, grant agreement no 733209; 2016). The researchers are independent from the funders. The study sponsors had no role in the study design, data collection and analysis, interpretation of data, writing of this report or the decision to submit the article for publication. The Generation R Study is conducted by the Erasmus Medical Centre in close collaboration with the School of Law and the Faculty of Social Sciences at the Erasmus University, Rotterdam, the Municipal Health Service, Rotterdam area, and the Stichting Trombosedienst and Artsen laboratorium Rijnmond (Star-MDC), Rotterdam. We gratefully acknowledge the contribution of children and their parents, general practitioners, hospitals, midwives and pharmacies in Rotterdam. Publisher Copyright: © 2020 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.

PY - 2020/4

Y1 - 2020/4

N2 - Background: Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection are common in early childhood. CMV infection favours a T-helper-1 and EBV infection a T-helper-2 cell response, possibly leading to disbalanced T-helper cell response, and subsequent risk of asthma or atopy. Objective: To study the associations of EBV and CMV with lung function, asthma and inhalant allergic sensitization at school age. Methods: This study among 3546 children was embedded in a population-based prospective cohort. At age 6 years, serum IgG levels against EBV and CMV were measured by ELISA. At age 10 years, lung function was measured by spirometry, asthma by questionnaire and inhalant allergic sensitization by skin prick test. Results: Unadjusted models showed that seropositivity for EBV was associated with a higher FEV1 and FEF75 (Z-score difference (95% CI): 0.09 (0.02, 0.16) and 0.09 (0.02, 0.15)), while seropositivity for CMV was not. Specific combinations of viruses showed that seropositivity for EBV was only associated with FEV1 and FEF75 in the presence of seropositivity for CMV (0.12 (0.04, 0.20)) and 0.08 (0.01, 0.15)). Seropositivity for CMV in the absence of seropositivity for EBV was associated with an increased risk of inhalant allergic sensitization (OR (95% CI): 1.31 (1.02, 1.68)). All effect estimates attenuated into non-significant mainly after adjustment for child's ethnicity. Seropositivity for EBV or CMV was not associated with asthma. Conclusions and Clinical Relevance: Associations of EBV and CMV infections in early childhood with school-age lung function and inhalant allergic sensitization are explained by ethnicity, or sociodemographic and lifestyle-related factors.

AB - Background: Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection are common in early childhood. CMV infection favours a T-helper-1 and EBV infection a T-helper-2 cell response, possibly leading to disbalanced T-helper cell response, and subsequent risk of asthma or atopy. Objective: To study the associations of EBV and CMV with lung function, asthma and inhalant allergic sensitization at school age. Methods: This study among 3546 children was embedded in a population-based prospective cohort. At age 6 years, serum IgG levels against EBV and CMV were measured by ELISA. At age 10 years, lung function was measured by spirometry, asthma by questionnaire and inhalant allergic sensitization by skin prick test. Results: Unadjusted models showed that seropositivity for EBV was associated with a higher FEV1 and FEF75 (Z-score difference (95% CI): 0.09 (0.02, 0.16) and 0.09 (0.02, 0.15)), while seropositivity for CMV was not. Specific combinations of viruses showed that seropositivity for EBV was only associated with FEV1 and FEF75 in the presence of seropositivity for CMV (0.12 (0.04, 0.20)) and 0.08 (0.01, 0.15)). Seropositivity for CMV in the absence of seropositivity for EBV was associated with an increased risk of inhalant allergic sensitization (OR (95% CI): 1.31 (1.02, 1.68)). All effect estimates attenuated into non-significant mainly after adjustment for child's ethnicity. Seropositivity for EBV or CMV was not associated with asthma. Conclusions and Clinical Relevance: Associations of EBV and CMV infections in early childhood with school-age lung function and inhalant allergic sensitization are explained by ethnicity, or sociodemographic and lifestyle-related factors.

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SN - 0954-7894

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JO - Clinical & Experimental Allergy

JF - Clinical & Experimental Allergy

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ER -

The influence of Epstein-Barr virus and cytomegalovirus on childhood respiratory health: A population-based prospective cohort study

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